A protocol has been developed with Lobund Sprague-Dawley (S-D) rats for experiments on chemically-induced autochthonous intestinal cancer. The S-D rat is highly susceptible to DMH and related agents, yielding reproducable and statistically-significant data in 20 weeks. Indomethacin (Indo) is useful because it blocks the synthesis of prostaglandins (PGs) at the cyclooxygenase level. It has interfered (a) with the development of intestinal tumors when administered as long as 35 days after DMH or MAM; and (b) with tumors induced by 4 agents, which suggests operation of a common drug-sensitive cancer-related factor(s). The Indo action is either antipromotional, antitumorigenic, or immunostimulatory. Tumors induced by a single marginal dose of DMH, MAM, or DMN Oac (and MNU) will be examined for PG production, and its modulation by Indo for possible less toxic piroxicam) administered in drinking water (20 mg/liter). The antitumor effect will be determined at various stages of tumorigenesis: with treatments at early, late, and intermediate stages of tumor development, in order to determine over longer periods of observation if tumors are only suppressed or actually prevented. PGE levels will be determined in serums and in tumors of Indo-treated and untreated rats. The promotional effect of high fat diets on tumor development will be assessed in DMH-treated rats in relation to production of PG, as well as bile acids. Groups of S-D rats, treated with DMH, will be fed diets high or low in fat; and subgroups therein will be treated with Indo in water. This is amined at clarification of whether the promotional effect is related to bile acids and/or to PG activities. PGs are produced by body cells, but in higher levels by tumor cells. Indo has demonstrated an anti-tumor effect. The goal of this research program is to determine if inhibition of PG synthesis by blocking agents is aimed at an intrinsic mechanism in tumor cells or is it merely a conincidental event, and unrelated to PG synthesis?